Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort

Shannon L. Risacher, Andrew Saykin, John D. West, Li Shen, Hiram A. Firpi, Brenna McDonald

Research output: Contribution to journalArticle

308 Citations (Scopus)

Abstract

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multi-center study assessing neuroimaging in diagnosis and longitudinal monitoring. Amnestic Mild Cognitive Impairment (MCI) often represents a prodromal form of dementia, conferring a 10-15% annual risk of converting to probable AD. We analyzed baseline 1.5T MRI scans in 693 participants from the ADNI cohort divided into four groups by baseline diagnosis and one year MCI to probable AD conversion status to identify neuroimaging phenotypes associated with MCI and AD and potential predictive markers of imminent conversion. MP-RAGE scans were analyzed using publicly available voxel-based morphometry (VBM) and automated parcellation methods. Measures included global and hippocampal grey matter (GM) density, hippocampal and amygdalar volumes, and cortical thickness values from entorhinal cortex and other temporal and parietal lobe regions. The overall pattern of structural MRI changes in MCI (n=339) and AD (n=148) compared to healthy controls (HC, n=206) was similar to prior findings in smaller samples. MCI-Converters (n=62) demonstrated a very similar pattern of atrophic changes to the AD group up to a year before meeting clinical criteria for AD. Finally, a comparison of effect sizes for contrasts between the MCI-Converters and MCI-Stable (n=277) groups on MRI metrics indicated that degree of neurodegeneration of medial temporal structures was the best antecedent MRI marker of imminent conversion, with decreased hippocampal volume (left > right) being the most robust. Validation of imaging biomarkers is important as they can help enrich clinical trials of disease modifying agents by identifying individuals at highest risk for progression to AD.

Original languageEnglish
Pages (from-to)347-361
Number of pages15
JournalCurrent Alzheimer Research
Volume6
Issue number4
DOIs
StatePublished - Aug 2009

Fingerprint

Neuroimaging
Alzheimer Disease
Parietal Lobe
Entorhinal Cortex
Temporal Lobe
Cognitive Dysfunction
Dementia
Biomarkers
Magnetic Resonance Imaging
Clinical Trials
Phenotype

Keywords

  • Alzheimer's disease neuroimaging initiative (ADNI)
  • Cognition
  • Hippocampus
  • Magnetic resonance imaging (MRI)
  • Mild cognitive impairment (MCI)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort. / Risacher, Shannon L.; Saykin, Andrew; West, John D.; Shen, Li; Firpi, Hiram A.; McDonald, Brenna.

In: Current Alzheimer Research, Vol. 6, No. 4, 08.2009, p. 347-361.

Research output: Contribution to journalArticle

@article{921f466008f049e7a74d0aed513f893c,
title = "Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort",
abstract = "The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multi-center study assessing neuroimaging in diagnosis and longitudinal monitoring. Amnestic Mild Cognitive Impairment (MCI) often represents a prodromal form of dementia, conferring a 10-15{\%} annual risk of converting to probable AD. We analyzed baseline 1.5T MRI scans in 693 participants from the ADNI cohort divided into four groups by baseline diagnosis and one year MCI to probable AD conversion status to identify neuroimaging phenotypes associated with MCI and AD and potential predictive markers of imminent conversion. MP-RAGE scans were analyzed using publicly available voxel-based morphometry (VBM) and automated parcellation methods. Measures included global and hippocampal grey matter (GM) density, hippocampal and amygdalar volumes, and cortical thickness values from entorhinal cortex and other temporal and parietal lobe regions. The overall pattern of structural MRI changes in MCI (n=339) and AD (n=148) compared to healthy controls (HC, n=206) was similar to prior findings in smaller samples. MCI-Converters (n=62) demonstrated a very similar pattern of atrophic changes to the AD group up to a year before meeting clinical criteria for AD. Finally, a comparison of effect sizes for contrasts between the MCI-Converters and MCI-Stable (n=277) groups on MRI metrics indicated that degree of neurodegeneration of medial temporal structures was the best antecedent MRI marker of imminent conversion, with decreased hippocampal volume (left > right) being the most robust. Validation of imaging biomarkers is important as they can help enrich clinical trials of disease modifying agents by identifying individuals at highest risk for progression to AD.",
keywords = "Alzheimer's disease neuroimaging initiative (ADNI), Cognition, Hippocampus, Magnetic resonance imaging (MRI), Mild cognitive impairment (MCI)",
author = "Risacher, {Shannon L.} and Andrew Saykin and West, {John D.} and Li Shen and Firpi, {Hiram A.} and Brenna McDonald",
year = "2009",
month = "8",
doi = "10.2174/156720509788929273",
language = "English",
volume = "6",
pages = "347--361",
journal = "Current Alzheimer Research",
issn = "1567-2050",
publisher = "Bentham Science Publishers B.V.",
number = "4",

}

TY - JOUR

T1 - Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort

AU - Risacher, Shannon L.

AU - Saykin, Andrew

AU - West, John D.

AU - Shen, Li

AU - Firpi, Hiram A.

AU - McDonald, Brenna

PY - 2009/8

Y1 - 2009/8

N2 - The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multi-center study assessing neuroimaging in diagnosis and longitudinal monitoring. Amnestic Mild Cognitive Impairment (MCI) often represents a prodromal form of dementia, conferring a 10-15% annual risk of converting to probable AD. We analyzed baseline 1.5T MRI scans in 693 participants from the ADNI cohort divided into four groups by baseline diagnosis and one year MCI to probable AD conversion status to identify neuroimaging phenotypes associated with MCI and AD and potential predictive markers of imminent conversion. MP-RAGE scans were analyzed using publicly available voxel-based morphometry (VBM) and automated parcellation methods. Measures included global and hippocampal grey matter (GM) density, hippocampal and amygdalar volumes, and cortical thickness values from entorhinal cortex and other temporal and parietal lobe regions. The overall pattern of structural MRI changes in MCI (n=339) and AD (n=148) compared to healthy controls (HC, n=206) was similar to prior findings in smaller samples. MCI-Converters (n=62) demonstrated a very similar pattern of atrophic changes to the AD group up to a year before meeting clinical criteria for AD. Finally, a comparison of effect sizes for contrasts between the MCI-Converters and MCI-Stable (n=277) groups on MRI metrics indicated that degree of neurodegeneration of medial temporal structures was the best antecedent MRI marker of imminent conversion, with decreased hippocampal volume (left > right) being the most robust. Validation of imaging biomarkers is important as they can help enrich clinical trials of disease modifying agents by identifying individuals at highest risk for progression to AD.

AB - The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multi-center study assessing neuroimaging in diagnosis and longitudinal monitoring. Amnestic Mild Cognitive Impairment (MCI) often represents a prodromal form of dementia, conferring a 10-15% annual risk of converting to probable AD. We analyzed baseline 1.5T MRI scans in 693 participants from the ADNI cohort divided into four groups by baseline diagnosis and one year MCI to probable AD conversion status to identify neuroimaging phenotypes associated with MCI and AD and potential predictive markers of imminent conversion. MP-RAGE scans were analyzed using publicly available voxel-based morphometry (VBM) and automated parcellation methods. Measures included global and hippocampal grey matter (GM) density, hippocampal and amygdalar volumes, and cortical thickness values from entorhinal cortex and other temporal and parietal lobe regions. The overall pattern of structural MRI changes in MCI (n=339) and AD (n=148) compared to healthy controls (HC, n=206) was similar to prior findings in smaller samples. MCI-Converters (n=62) demonstrated a very similar pattern of atrophic changes to the AD group up to a year before meeting clinical criteria for AD. Finally, a comparison of effect sizes for contrasts between the MCI-Converters and MCI-Stable (n=277) groups on MRI metrics indicated that degree of neurodegeneration of medial temporal structures was the best antecedent MRI marker of imminent conversion, with decreased hippocampal volume (left > right) being the most robust. Validation of imaging biomarkers is important as they can help enrich clinical trials of disease modifying agents by identifying individuals at highest risk for progression to AD.

KW - Alzheimer's disease neuroimaging initiative (ADNI)

KW - Cognition

KW - Hippocampus

KW - Magnetic resonance imaging (MRI)

KW - Mild cognitive impairment (MCI)

UR - http://www.scopus.com/inward/record.url?scp=69149094447&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69149094447&partnerID=8YFLogxK

U2 - 10.2174/156720509788929273

DO - 10.2174/156720509788929273

M3 - Article

VL - 6

SP - 347

EP - 361

JO - Current Alzheimer Research

JF - Current Alzheimer Research

SN - 1567-2050

IS - 4

ER -